Gamma linolenic acid (GLA) is a dietary omega-6 fatty acid found in many plant oil extracts. Commercial products are typically made from seed extracts from evening primrose (average oil content 7-14%), blackcurrant (15-20%), borage oil (20-27%) and fungal oil (25%). GLA is not found in high levels in the diet. It has been suggested that some individuals may not convert the omega-6 fatty acid linoleic acid to longer chain derivatives, such as GLA, efficiently. Thus, supplementation with GLA-containing oils, such as borage oil and evening primrose oil, is occasionally recommended to increase GLA levels in the body.

GLA is available commonly as a dietary supplement and is sold over the counter in capsules or oil to treat a variety of conditions such as eczema, oral mucoceles (mucus polyps), hyperlipidemia (high cholesterol), depression, postpartum depression, chronic fatigue syndrome (CFS), psoriasis (chronic skin disease), muscle aches, and menopausal flushing.

There is currently good evidence for GLA treatment in rheumatoid arthritis, acute respiratory distress syndrome, and diabetic neuropathy (nerve damage). Little or no effect has been found in treatment of atopic dermatitis, attention deficit hyperactivity disorder (ADHD), cancer prevention, menopausal flushing, systemic sclerosis, and hypertension (high blood pressure). GLA has also been used to help with the body's response to tamoxifen in breast cancer patients.

Today, production and extraction of oil from evening primrose and borage is done by companies primarily in China, New Zealand, and England. Pharmaceutical licensing for GLA oil products has had only limited success worldwide.

These uses have been tested in humans or animals. Safety and effectiveness have not always been proven. Some of these conditions are potentially serious, and should be evaluated by a qualified healthcare provider.

GRADE *

Diabetic neuropathy is a degenerative state of the nervous system that causes a variety of pain, tingling, burning, numbness and resultant loss of balance. The most common type, which is said to affect nearly half of diabetic patients, is distal polyneuropathy, which affects the peripheral nervous system in the legs, feet, arms, and hands. GLA may be a viable treatment, although additional study is needed in this area to confirm these findings.

B

Acute respiratory distress syndrome is respiratory failure in adults or children resulting in diffuse injury to the alveoli (tiny air scas) and lung capillary endothelium. GLA may promote the production of prostaglandin E1, an eicosanoid with known anti-inflammatory and immunoregulatory properties, which in turn may aid in treating ARDS. Additional study is warranted in this area.

C

Atopic dermatitis (AD) is one of the most common chronic inflammatory skin diseases, associated with at least 10% of children and 0.5-1% of adults. Studies in the past 20 years reveal minimal therapeutic improvements with GLA as therapy for atopic dermatitis, noted by only marginal to no improvement in inflammation and itching.

C

Clinical trials investigating the effect of GLA on symptoms associated with attention-deficit disorder are limited. There is no evidence of effectiveness of treatment with GLA, but more study is needed to confirm these results.

C

Preliminary study has investigated GLA on blood pressure changes. The evidence suggests that GLA may offer benefits in terms of blood pressure reduction; however, better-designed trials are required before definite conclusions can be made.

C

Preliminary study has indicated that GLA may act as a cytotoxic agent or at least as an adjunct agent to a chemotherapy regimen. However, human studies are conflicting and more study is needed before a strong conclusion can be made.

C

Few clinical trials have investigated the effect of GLA on immune responses in healthy human subjects. GLA, as blackcurrant seed oil, may offer some benefits. Further study is required before a definite conclusion can be made.

C

Cyclical mastalgia is breast pain experienced by women and typically associated with the menstrual cycle. The pain can vary in severity and usually occurs between ovulation and menstruation. Evidence for efficacy of GLA treatment is very limited, although since the 1990s, GLA has been recommended historically as a therapy.

C

One study has examined the effect of GLA (evening primrose oil) on menopausal flushing. No improvement in the number of flushes was noted as compared with placebo. More clinical trials are needed before a strong recommendation can be made in this area.

C

Preliminary study has examined the effect of fatty acids, including GLA, on severity, frequency and duration of migraine attacks. Better-designed clinical trials are required before a strong recommendation can be made.

C

Some evidence from a clinical trial and observations of clinicians and dieticians has suggested that GLA and eicosapentaenoic acid (EPA) enhance the effects of calcium supplementation in elderly patients with senile osteoporosis. More clinical studies are required to produce results to determine effectiveness in diverse elderly and middle-age populations.

C

A study of GLA plus fish oil suggests there is a potential for benefit of edema (sweeling) in pregnancy. Clinical trials investigating the effects of GLA alone is required before a strong recommendation can be made.

C

A study using Efamol (containing GLA) suggests there may be benefit in terms of premenstrual syndrome symptoms. More information is needed in this area before a firm recommendation can be made.

C

Abnormalities of plasma fatty acids may be associated with pruritus (severe itching) in patients undergoing hemodialysis. GLA as evening primrose oil may improve skin conditions in these patients. Further clinical trials are required before a strong recommendation can be made.

C

Several clinical studies indicate significant therapeutic improvements in rheumatoid arthritis symptoms through reductions in scores on joint tenderness, joint swelling, physician global assessment and pain. Some studies also suggest that GLA may be a more tolerable alternative to the standard pain-reduction therapies, such as COX / COX2 inhibitors, and NSAIDs and their adverse events. However, there is some concern on dosage control and additional study is needed to make a strong recommendation in this area.

C

Currently, there is limited evidence showing that GLA is effective in treating Sjogren's syndrome. Additional study is needed before a firm recommendation can be made.

C

Currently, there is insufficient available evidence supporting the use of gamma linolenic acid for ulcerative colitis. Additional study is warranted.

C

* Key to grades

A: Strong scientific evidence for this useB: Good scientific evidence for this useC: Unclear scientific evidence for this useD: Fair scientific evidence for this use (it may not work)F: Strong scientific evidence against this use (it likley does not work)

Tradition / Theory
The below uses are based on tradition, scientific theories, or limited research. They often have not been thoroughly tested in humans, and safety and effectiveness have not always been proven. Some of these conditions are potentially serious, and should be evaluated by a qualified healthcare provider. There may be other proposed uses that are not listed below.

There is no proven effective dose for GLA in adults. GLA is likely safe when taken by mouth short-term (up to 18 months) in recommended doses. GLA is possibly safe when used long term (up to 36 months). Doses as high as 6 grams per day have been taken for treatment of hyperlipidemia (high cholesterol), and dose as high as 2.8 grams have been taken for rheumatoid arthritis and as an adjuvant treatment with tamoxifen, although there is some concern that these high levels may have adverse effects. However, studies following patients taking large doses, for example, 1.4g to 2.8 grams per day for up to one year, have found GLA to be non-toxic.

Common doses of GLA range between 500-1,000 milligrams per day. For atopic eczema, up to 920 milligrams has been taken daily. For diabetic neuropathy, up to 480 milligrams has been taken daily. Intravenous preparations (injections) have also been studied, although injections should only be given under the supervision of a qualified healthcare professional, including a pharmacist.

Children (under 18 years old)

There is no proven safe or effective dose for GLA in children. However, for atopic eczema, 360-460 milligrams daily has been used.

Safety
The U.S. Food and Drug Administration does not strictly regulate herbs and supplements. There is no guarantee of strength, purity or safety of products, and effects may vary. You should always read product labels. If you have a medical condition, or are taking other drugs, herbs, or supplements, you should speak with a qualified healthcare provider before starting a new therapy. Consult a healthcare provider immediately if you experience side effects.

Allergies

Avoid in individuals with allergy or sensitivity to gamma linolenic acid. However, no reports of allergy or hypersensitivity have been reported in the available literature.

Side Effects and Warnings

GLA is generally considered nontoxic and well tolerated for up to 18 months. Possible side effects may include upset and bloated stomach, soft stool, nausea and vomiting, flatulence (gas) and belching.

Supplementation with GLA at high levels and for a long duration has been suggested to produce excess levels of arachidonic acid. Chronic use may result in changes in the blood and increase bleeding time. However, studies of diets rich in GLA did not reveal any significant change in blood parameters. Until more research resolves this controversy, caution is advised in those using anticoagulant or antiplatelet (blood thinning) agents.

Pregnancy and Breastfeeding

GLA is not recommended in pregnant or breastfeeding women due to a lack of available scientific evidence.

GLA may increase the risk of bleeding when taken with drugs that increase the risk of bleeding. Some examples include aspirin, anticoagulants ("blood thinners") such as warfarin (Coumadin®) or heparin, anti-platelet drugs such as clopidogrel (Plavix®), and non-steroidal anti-inflammatory drugs (NSAIDS) such as ibuprofen (Motrin®, Advil®) or naproxen (Naprosyn®, Aleve®).

Theoretically, GLA may increase the effectiveness of ceftazidime, an antibiotic in a class known as cephalosporins, against a variety of bacterial infections. It is unknown whether effectiveness of other cephalosporin antibiotics are likewise affected.

GLA may alter the effects of certain anti-cancer treatments. Caution is advised.

Theoretically, taking omega-6 fatty acids, such as GLA, during therapy with cyclosporine, a medication used to suppress the immune system after an organ transplant, for example, may increase the immunosuppressive effects of cyclosporine and may protect against kidney damage associated with cyclosporine.

Individuals taking phenothiazines (such as chlorpromazine, fluphenazine, perphenazine, promazine, and thioridazine) to treat schizophrenia should not take evening primrose oil, a source of GLA, because it may interact with these medications and increase the risk of seizures. Theoretically, the same may be true for other GLA containing supplements.

Interactions with Herbs and Dietary Supplements

GLA may increase the risk of bleeding when taken with herbs and supplements that are believed to increase the risk of bleeding. Multiple cases of bleeding have been reported with the use of Ginkgo biloba, and fewer cases with garlic and saw palmetto. Numerous other agents may theoretically increase the risk of bleeding, although this has not been proven in most cases.

Although not well studied in humans, coenzyme Q10 and vitamin E reversed the inhibition of cell growth associated with GLA. Thus, nutritional antioxidants may inhibit certain effects associated with GLA.

The information in this monograph is intended for informational purposes only, and is meant to help users better understand health concerns. Information is based on review of scientific research data, historical practice patterns, and clinical experience. This information should not be interpreted as specific medical advice. Users should consult with a qualified healthcare provider for specific questions regarding therapies, diagnosis and/or health conditions, prior to making therapeutic decisions.